The invention relates to an apparatus for separating magnetic particles in suspension in a liquid contained in a reaction vessel of the type used in an automatic apparatus for processing biological samples, said processing including introducing a sample and one or more reagents into the reaction vessel.
Magnetic particles are used as solid phase for performing some diagnostic assays, e.g. immunoassays. Such assays comprise magnetic particles in suspension in a reaction solution contained in a reaction vessel. When the assay is conducted, it may be necessary to separate the magnetic particles from the liquid contained in the reaction vessel. In known apparatus this is usually done by attracting the magnetic particles to the walls of the reaction vessel by means of magnets positioned close to the outer side wall of the reaction vessel and by extracting the liquid from the reaction vessel by suitable means. This separation step is usually followed by a so called washing step in which the magnets are withdrawn to eliminate the magnetic force which held the magnetic particles on the inner wall of the reaction vessel during the previous separation step and fresh liquid pipetted into the reaction vessel in a way suitable to cause resuspension of the magnetic particles in the liquid contained in the reaction vessel.
A disadvantage of known apparatuses for performing the above-described separation step is that the relative movement of the magnet or magnets with respect to the reaction vessel is a translational movement and this has the disadvantage that the magnetic force exerted on the magnetic particles cannot be quickly removed and this causes an undesirable delay of the resuspension step. According to WO-A-96/31781 this latter disadvantage can be overcome by moving the magnet or magnets along a circular path.
In known apparatuses for performing the above-described separation step, the magnet or magnets used therefor are positioned always at the same position. This has the disadvantage that the separation step can be carried out properly and fast enough only for a limited variation range of the amount of the reaction solution contained in the reaction vessel. Outside that limited range the separation step is too slow.
A main object of the invention, therefore, is to provide an apparatus to overcome the above mentioned disadvantages of prior art apparatuses.
A further object of the invention is to provide an apparatus which is also suitable for performing not only the above described separation step, but also a washing step.
According to the invention, this problem is solved by an apparatus which comprises
a) a carrier holding an array of magnet elements; said carrier being rotatable about a rotation axis,
b) said array of magnet elements comprising a first magnet element and at least a second magnet element,
said first and second magnet elements being positioned on the carrier at different distances from the rotation axis and the centers of the first magnet element and of the second magnet element lying on radii located at different azimuth angles,
the carrier and the array of magnet elements being so configured and dimensioned that
by rotation of the carrier the first magnet element can be positioned close to the external surface of a side wall of the reaction vessel on one side thereof and at a first predetermined height with respect to the bottom of the reaction vessel, and that
by further rotation of the carrier of a predetermined angle the at least second magnet element can be positioned close to said external surface of the side wall of the reaction vessel at a second predetermined height with respect to the bottom of the reaction vessel, said second predetermined height being different from said first predetermined height, and
c) means for selectively positioning said carrier and thereby said array of magnet elements at a plurality of predetermined angular positions.
The main advantage of the apparatus according to the invention as compared with the prior art is that it enables a fast separation of magnetic particles contained in suspension in a reaction solution contained in a reaction vessel. This fast separation is obtained by rapid positioning of magnets close to the reaction vessel and at a plurality of selected heights with respect to the bottom of the reaction vessel. The height at which a magnet is positioned at a given point of time being selected according to a processing step to be carried out in the reaction vessel and/or according to the amount of reaction solution contained in the reaction vessel. This permits optimum adaptation of magnetic particle separation step to the process step being carried out in the reaction vessel.
A further advantage of the apparatus according to the invention is that it also enables rapid removal of magnets positioned close to the reaction vessel during a separation step. This rapid removal reduces the time interval necessary to obtain a resuspension of the magnetic particles in liquid contained in the reaction vessel.
A preferred embodiment of the apparatus according to the invention is characterized in that it comprises
a) a first carrier holding a first array of magnet elements; said first carrier being rotatable about a first rotation axis,
b) a second carrier holding a second array of magnet elements; said second carrier being rotatable about a second rotation axis,
c) said first and second carriers being so connected with each other that rotation of one the carriers through a predetermined angle causes rotation of the other carrier of the same angle,
d) each of said first and second arrays of magnet elements comprising a first magnet element and at least a second magnet element, said first and second magnet elements being positioned on the carrier at different distances from the rotation axis of the respective carrier of the array of magnet elements and the centers of the first magnet element and of the second magnet element lying on radii located at different azimuth angles, the carriers and the arrays of magnet elements being so configured and dimensioned that
by rotation of the carriers, one or more of the magnet elements of the first array of magnet elements can be positioned close the external surface of the side wall of the reaction vessel on one side thereof and/or
one or more of the magnet elements of the second array of magnet elements can be positioned close to the external surface of the side wall of the reaction vessel on the opposite side thereof, and that
by further rotation of the carriers through a predetermined angle other magnet element or elements of the first array of magnet elements can be positioned close to the external surface of the side wall of the reaction vessel on one side thereof and/or
other magnet element or elements of the second array of magnet elements can be positioned close to the external surface of the side wall of the reaction vessel on the opposite side thereof, and
e) means for selectively positioning said first and second carriers and thereby said first and second arrays of magnet elements at a plurality of predetermined angular positions.
The advantage of this preferred embodiment is that the combined effect of magnets positioned on opposite sides of a reaction vessel makes it possible to obtain a fast separation of magnetic particles contained in suspension in a reaction solution contained in a reaction vessel, even in a wide vessel.
A further preferred embodiment of the apparatus according to the invention comprises
a) a first carrier holding a first array of magnet elements; said first carrier being rotatable about a first rotation axis,
b) a second carrier holding a second array of magnet elements; said second carrier being rotatable about a second rotation axis,
c) said first and second carriers being so connected with each other that rotation of one the carriers of a predetermined angle causes rotation of the other carrier of the same angle,
d) each of said first and second arrays of magnet elements comprising a first magnet element and at least a second magnet element,
said first and second magnet elements being positioned on the carrier which holds the array at different distances from the rotation axis of the carrier and the centers of the first magnet element and of the second magnet element lying on radii located at different azimuth angles,
said first and second carrier and the arrays of magnet elements they hold being so configured and dimensioned that
by rotation of the carriers, one or more of the magnet elements of the first array of magnet elements can be positioned close to the external surface of the side wall of the reaction vessel on one side thereof, and that
by further rotation of the carriers of a predetermined angle, one or more of the magnet elements of the second array of magnet elements can be positioned close to the external surface of the side wall of the reaction vessel on the opposite side thereof,
whereby one or more magnet elements are alternatively positioned close to the external surface of the side wall of the reaction vessel either on one side or on the opposite side thereof, simultaneous positioning of magnet elements close to the external surface of the side wall of the reaction vessel on both sides thereof being excluded, and
e) means for selectively positioning said first and second carriers and thereby said first and second arrays of magnet elements at a plurality of predetermined angular positions.
The advantage of this preferred embodiment is that it enables a washing step, that is a washing of the magnetic particles in suspension in a liquid, e.g. water, contained in a reaction vessel, by alternatively positioning a magnet or an array of magnet elements either on one side of the vessel or on the opposite side of the vessel, and thereby causing migration of the magnetic particles through the liquid from one side of the vessel to the opposite side thereof, the sense of this migration being reversed by changing the side on which a magnet is positioned close to the vessel.
Another preferred embodiment of the apparatus according to the invention is characterized in that each of the magnet elements of said array or arrays of magnet elements comprises one or more magnets having the same width and the same azimuthal position on the carrier of the array.
A further preferred embodiment of the apparatus according to the invention is characterized in that the axis of rotation of the carrier, respectively of each of the carriers, intersects with the length axis of the reaction vessel at a point located below the bottom of the reaction vessel.
A further preferred embodiment of the apparatus according to the invention comprising a first and a second rotatable carrier is characterized in that the axis of rotation of the carriers form an angle which is in the range between 170-175 degrees. In an alternative preferred embodiment the carriers have a common axis of rotation.
A further preferred embodiment of the apparatus according to the invention is characterized in that said means for selectively positioning said carrier or carriers are apt to position said carrier or carriers at predetermined angular positions which are selected according to a processing step to be carried out in that reaction vessel and/or according to the amount of liquid in the reaction vessel.
A further preferred embodiment of the apparatus according to the invention is characterized in that said plurality of predetermined angular positions include one position at which no magnet element of said array or arrays of magnet elements is located close to any external surface of the reaction vessel.